Sodium Carbonate → 5-(4-Fluorophenyl)pyridin-2-amine

Participants

Reaction Steps

To a mixture of 2-amino-5-bromopyridine 1 (1.80 g, 10.4 mmol) in 104 ml toluene and 24 ml ethanol (EtOH) was added 4-fluorophenyl boronic acid (1.75 g, 12.5 mmol) followed by 10 ml of 2.0 M aqueous Na2CO3. The reaction was degassed with nitrogen and Pd(PPh3)4 (0.60 g, 0.52 mmol) was added in one portion and the reaction was heated to reflux for 26 hours. The reaction was then cooled to ambient temperature and diluted with 50 ml water. The layers were separated and the aqueous layer was extracted with ethyl acetate (EtOAc) (2×100 mL). The organic layers were combined, washed with saturated aqueous NaHCO3, dried over MgSO4 and concentrated to a brown oil. Automated purification on a silica gel ISCO column (120 g column, 2.5% MeOH—CH2Cl2) gave 1.20 g (60%) of 2-amino-5-(4-fluorophenyl)pyridine as a yellow solid.

Provenance & Evidence